Synthesis and Anti-HCV Activity of 4-Hydroxyamino α-Pyranone Carboxamide Analogues
- ACS Med Chem Lett. 2013 Dec 3;5(3):259-63. doi: 10.1021/ml400432f.
- 1. Department of Applied Chemistry, Birla Institute of Technology , Mesra, Ranchi, Jharkhand, India.
- 2. Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Kagoshima University , Kagoshima, Japan.
High genetic variability in hepatitis C virus (HCV), emergence of drug resistant viruses and side effects demand the requirement for development of new scaffolds to show an alternate mechanism. Herein, we report discovery of new scaffold I based on 4-hydroxyamino α-pyranone carboxamide as promising anti-HCV agents. A comprehensive structure-activity relationship (SAR) was explored with several newly synthesized compounds. In all promising compounds (17-19, 21-22, 24-25, and 49) with EC50 ranging 0.15 to 0.40 μM, the aryl group at C-6 position of α-pyranone were unsubstituted. In particular, 25 demonstrated potential anti-HCV activity with EC50 of 0.18 μM in cell based HCV replicon system with lower cytotoxicity (CC50 > 20 μM) and provided a new scaffold for anti-HCV drug development. Further investigations, including biochemical characterization, are yet to be performed to elucidate its possible mode of action.